Lenalidomide enhancement of human T cell functions in human immunodeficiency virus (HIV)-infected and HIV-negative CD4 T lymphocytopenic patients

H. Lim, L. Kane, J. B. Schwartz, C. S. Hesdorffer, S. G. Deeks, N. Greig, L. Ferrucci, E. J. Goetzl

Research output: Contribution to journalArticlepeer-review

Abstract

Suppressed T cell functions in human immunodeficiency virus (HIV) infection were identified and corrected by lenalidomide in middle-aged HIV-infected patients. Chemotaxis of T cells from HIV-infected men (n=6, mean 43 years) to sphingosine 1-phosphate (S1P) and CCL21 was significantly lower than that of HIV-negative men (n=6, mean 41 years), and was enhanced significantly up to control levels by 100 and 1000nM lenalidomide. Generation of interleukin (IL)-2, but not interferon (IFN)-γ, by T cells of middle-aged HIV-infected men was significantly lower than that for controls and was increased significantly by 10-1000nM lenalidomide up to a maximum of more than 300%. CD4 and CD8 T cells isolated from healthy middle-aged men and reconstituted in vitro at a low CD4:CD8 ratio typical of HIV infection had depressed chemotaxis to S1P, but not CCL21, and generation of IL-2, but not IFN-γ. Significant enhancement of chemotaxis to S1P and CCL21was induced by 100-1000nM lenalidomide only for normal T cells at a low CD4:CD8 ratio. T cells from HIV-negative middle-aged CD4 T lymphocytopenic patients (n=3), with a CD4:CD8 ratio as low as that of HIV-infected patients, had similarly diminished chemotaxis to S1P and CCL21, and depressed generation of IL-2, but not IFN-γ. Lenalidomide at 30-1000nM significantly enhanced chemotaxis to S1P and IL-2 generation for T cells from HIV-negative CD4 T lymphocytopenic patients as from HIV-infected patients, with less effect on CCL21-elicited chemotaxis and none for IFN-γ generation. Defects in functions of T cells from middle-aged HIV-infected men are partially attributable to CD4 T lymphocytopenia and are corrected by lenalidomide.

Original languageEnglish (US)
Pages (from-to)182-189
Number of pages8
JournalClinical and Experimental Immunology
Volume169
Issue number2
DOIs
StatePublished - Aug 2012

Keywords

  • AIDS
  • Chemotaxis
  • Cytokines
  • Immunopharmacology
  • T lymphocytes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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